Multi-Dimensional Cross-Reactive Array for Chemical Sensing

ABSTRACT

The discrimination ability of a chemical sensing cross-reactive arrays is enhanced by constructing sensing elements in two dimensions, first in the x-y plane of the substrate, second in the z dimension so that the sensors are vertically stacked on top of one another. Stacking sensing elements on top of one another adds to the discrimination ability by enabling the characteristic measurement of how fast target chemicals are passing through the stack of sensors. The new invention also allows the ability to discriminate components in a sample mixture by separating them using their innate difference in diffusional rates. Multi-sensor response patterns at each z level of sensors and time delay information from the sample passing from one level to the next are used to generate the response vector. The response vector is used to identify individual component samples and components in a mixture sample.

GOVERNMENT INTEREST

The invention described herein may be manufactured, used, sold,imported, and/or licensed by or for the Government of the United Statesof America.

FIELD OF THE INVENTION

This invention relates in general to cross-reactive arrays for chemicalsensing, and more particularly to multi-dimensional cross-reactivearrays for sensing explosive threats, chemical warfare agents, and toxicindustrial chemicals.

BACKGROUND OF THE INVENTION

A cross-reactive array sensor is a device that mimics the sense of smellin mammals. It is generally thought that mammal's sense of smell, whichis called olfaction, operates by the brain interpreting a complexpatterned response from the olfactory bulb where odors interact withbetween 800-1200 different receptors. Each receptor in the olfactorybulb is slightly different so that when they all interact with the sameodor they all respond slightly different making a pattern that ischaracteristic of that odor. Due the different chemical nature of eachodor the olfactory bulb makes a unique pattern for each odor that isable to be distinguished.

Cross-reactive arrays mimic the sense of smell by using more than onebroadly responsive (non-specific) chemical sensor to generate apatterned response which is then interpreted by a computer algorithm toidentify the chemical being interrogated. These have been made usingmany different sensing methods including tin oxide sensors, carbon blackpolymer composites, fluorescent polymers, carbon nanotubes, inorganicdyes, quantum dots, functionalized metallic nanoparticles, and others. Afew good references on these type of devices are, e.g., Anzenbacher,Jr., P., Lubal, P., Bu{hacek over (c)}ek, P., Palacios, M. A. &Kozelkova, M. E. A practical approach to optical cross-reactive sensorarrays. Chem. Soc. Rev. 39, 3954 (2010); and Albert, K. J. et al.Cross-Reactive Chemical Sensor Arrays. Chem. Rev. 100, 2595-2626 (2000).

All of the previous examples of cross-reactive arrays placed the sensingelements on the same plane where they interact with the sample.Additionally, all cross-reactive arrays are poor at identifyingcomponents in a mixture sample. This invention is similar but differentthan U.S. Pat. No. 7,189,353 B2. U.S. Pat. No. 7,189,353, entitled, “Useof spatiotemporal response behavior in sensor arrays to detect analytesin fluids,” discloses a time delay feature added to the feature vectorfor added discrimination ability and components in a mixture cantheoretically be discriminated.

Other references worth mentioning are Cross-reactive sensors, U.S. Pat.No. 7,250,267 B2 issued to Walt et al.; and Method for determininganalyte concentration by cross-reactivity profiling, U.S. Pat. No.5,338,659 A issued to Kauvar et al.

SUMMARY OF THE INVENTION

The disclosure relates to fabricating a chemical sensor that can be usedby the Army to sense explosive threats, chemical warfare agents, andtoxic industrial chemicals. It may be used by the food and beverageindustries in quality control relating to spoilage, ripeness, anduniformity of a manufactured item. The disclosure may also findrelevance in medical uses as a diagnostic tool for detecting disease.

Other devices of this type are referred to as cross-reactive arrays,electronic noses, and multiplexed sensors. Cross-reactive arrays aredisclosed with out-of-plane stacking of sensors to generatetime-dependent responses, which are then combined with different z-levelarray descriptors. Additionally, diffusion of volatile chemicals throughsolid medium is much slower than through gas or liquid, making aneffective device for identifying mixture samples much smaller. Thedevice is smaller because a slower diffusion rate makes the distanceneeded to separate components in a mixture much shorter.

Methods of making artificial olfactory systems rely on non-specificsensors which respond in concert generating a pattern that can beidentified as the odorant impinging upon the sensor. The responsepattern is formed by using chemically different sensors whose responseto a single analyte is varied. The difference of the sensors on themolecular level generates the varying changes in the transduction, andfeatures such as total magnitude of response, percent change ofresponse, and amount of spectral change are used to make the descriptivepattern response.

This invention adds more descriptive information to the response patternby arranging the elements of a cross-reactive array in a 2 dimensionalmanner, the first dimension is the direction of the sample flow in thesensor so that the sample interacts with each sensor in a sequentialmanner through the gas or liquid sample carrier medium. The firstdimension is in the x and y plane of the substrate that the device isconstructed on. The stacking of the sensors happens in the z dimensionof the substrate. The sensors are stacked in intimate contact one on topof another so that the only way for a sample to interact with underlyingsensors it to pass through the sensor on top of it. The stacking of thesensors adds a time dependent response to the underlying sensors basedupon the diffusion the sample through the sensor layers. The diffusiontime of the samples through the sensor is based upon the thickness ofthe sensor layers, density of the sensor layer, and chemicalinteractions that take place. The information added to the responsepattern is the diffusion constants, and difference in time it takes foreach sensor to respond. The diffusion constant and time delay are twocharacteristic features that can be added to the response pattern fordiscrimination.

This type of device can be constructed with any of the previouslyreported sensor types that are permeable to volatile chemicals.

BRIEF DESCRIPTION OF THE DRAWINGS

Additional advantages and features will become apparent as the subjectinvention becomes better understood by reference to the followingdetailed description when considered in conjunction with theaccompanying drawings wherein:

FIG. 1 shows an exemplary 2-dimensional cross-reactive array having asensor substrate in an enclosure.

FIG. 2 shows an exemplary z-dimensional stacking of sensor elements.

FIG. 3 shows a schematic of an exemplary three polymer system excitationusing a light source such as a 365 nm LED.

FIG. 4 shows exemplary spectral bands of three fluorescent polymersystem.

FIG. 5 shows exemplary z-stacked sensors in which a non-responsivepermeable buffer layer is added in between sensor layers.

FIG. 6a shows exemplary stacked sensor layers spaced in the x and ydirection by impermeable blocking layers.

FIG. 6b shows an alternate stacking sensor layering in which successivesensor layer each completely covers the sensor layer below.

DETAILED DESCRIPTION

Methods of making artificial olfactory systems (cross-reactive arrays)rely on non-specific sensors which respond in concert generating apattern that can be identified as the odorant impinging upon the sensor.The response pattern is formed by using chemically different sensors whoresponse to a single analyte is varied. The difference of the sensors onthe molecular level generates the varying changes in the transductionand features such as total magnitude of response, percent change ofresponse, fitting of polynomial lines, and amount of spectral change areused to make the descriptive response patterns.

This invention adds more descriptive information to the response patternby arranging the elements of a cross-reactive array in a 2 dimensionalmanner, the first dimension is the direction of the sample flow in thesensor so that the sample interacts with each sensor in a sequentialmanner through the gas or liquid sample carrier medium. This is shown inFIG. 1 where 1 the sensor substrate which can be quartz for opticalbased sensors or silicon for electrical based sensors is in an enclosure2. The areas where the stacks of sensor elements are laid out so thatthe flow interacts with them sequentially in the flow path are show aselements 3-8. The first dimension is in the x and y plane of thesubstrate that the device is constructed on. The stacking of the sensorshappens in the z-dimension of the substrate shown in FIG. 2 whereelements 9-14 are stacks of sensing elements. In this exemplaryembodiment, the sensors are stacked in intimate contact one on top ofanother so that the only way for a sample to interact with underlyingsensors is to pass through the sensor on top of it. The stacking of thesensors adds a time dependent response to the underlying sensors basedupon diffusion of the sample through the upper sensor layers. Thesensors in each z-stack have to be responsive to the same classes ofchemicals so that the passage of a chemical from one layer to the nextcan be measured. Each sensor in the z-stacked also needs to beindividually addressable so each one can be monitored for changes overtime. A way to make a stack of individually addressable stacked sensorsis to use fluorescent polymers whose emission intensity is dependent ontheir local environment. Each of the fluorescent polymers in the z-stackhave to have emission spectrums that are spectrally separated enough tomonitor each emission peak with a spectrometer. An example of this typeof fluorescent polymer z-stack are these three polymers;Poly[2,5-bisoctyloxy)-1,4-phenylenevinylene] (P1) with a emissionbetween 540-560 nm, Poly(9,9-dioctylfluorene-alt-benzothiadiazole) (P2)with emission between 515-535 nm andPoly[(9,9-dihexylfluoren-2,7-diyl)-co-(anthracen-9,10-diyl)] (P3) withemission between 450-435 nm. This three polymer system is also excitablewith a common light source such as a 365 nm LED. A schematic of thisdevice is in FIG. 3, where 15 is an excitation light source such as a365 nm LED. The light source 15 is focused onto the polymers P1-P3causing them to emit fluorescence which is collected by an opticalsystem such as a fiber optic cable seen as elements 16-21 which passesthe emitted light from each stack of sensors to a separate spectrometerelements 22-27. All of the spectrometers are connected to a computerelement 28 which is used to select wavelength bands from eachspectrometer output characteristic of each fluorescent polymer in thesensor stacks for each stack throughout the array. The spectrumsmeasured by each spectrometer and the selected spectral bands of thisthree fluorescent polymer system are shown in FIG. 4. Where elements29-31 are the fluorescence emission spectrums of P1-P3 respectively. Thebands which are monitored to characterize the different fluorescentpolymers are indicate in elements 32-34. In addition to these polymersbeing individually addressable with a spectrometer they are sostructurally different enough to provide a robust cross-reactive arrayresponse.

A second method of making a z-stack of fluorescent sensors is to use afluorescent nanocrystal/polymer composite. Fluorescence emission fromnanocrystals is a size dependent property with narrow emissionspectrums. The nanocrystals narrow emission spectrums allow more sensorsto be stacked in the z-direction and still be able to be spectrallyresolved using a spectrometer. A z-stack sensor array can be constructedusing a set of CdSe nanocrystals of sizes 2.2, 2.5 3.3, 4.5 nm withemission maxima of 480, 520, 560, 600 nm respectively in the same manneras FIGS. 3 and 4. This set of nanocrystal can then be mixed with anynon-fluorescent polymer to add chemical diversity such as this set,Poly(vinyl stearate), Poly(benzyl methacrylate), Poly(methylmethacrylate), Poly(ethylene-co-vinyl acetate). Each stack of sensors inmust only contain one composite of each size nanocrystal so thatdifferent layers of the stack can be monitored independently.

A third way of making individually addressable sensor is to use a stackof chemiresistors with insulating buffer layer in between them. Anexample of chemiresistor chemical sensor suitable for z-stacking includemodified carbon nanotubes, carbon nanotube polymer composites, andpolymer carbon black composites.

In all iterations of z-stacked sensors a non-responsive permeable bufferlayer can be added in between the sensor layer to increase the migrationtime between sensors as seen in FIG. 5. Where elements 35, 37, 39, 40,42, and 44 are sensors and elements 36, 38, 41, and 43 are permeablebuffer layers. The buffer layers increase the resolution ofmulti-analyte samples by increasing the time selective differentialpartitioning happens between sensors. Buffer layers can include neatforms of the polymers used in the sensing composites or other types ofpolymers such as siloxanes used in gas chromatography. The diffusiontime of the samples through the sensor is based upon the thickness ofthe sensor layers, density of the sensor layer, chemical interactionsthat take place, and the time added for the sample to pass through thebuffer layer.

There are several methods for constructing an array of z-stacked sensorsincluding, stamping, thermal evaporation, and inkjet printing. Stampingof the fluorescent polymer and polymer composite materials is done witha polydimethlsiloxane made with Dow Corning Sylgard 184 with is castonto a template of the desired sensor size and allowed to cure. Thecured stamp then has the fluorescent polymer or polymer composite spuncast onto it from a solvent. The solvent is evaporated from the stampleaving a layer of the sensing material. The inked stamp is then placedsensor side down on the sensor substrate and heated above the glasstransition temperature of the polymer. The stamp is then removed fromthe substrate leaving behind the sensor layer. This stamping process isrepeated with different sensing layers in the same location on thesubstrate to form the z-stacked sensor array. Stamping can also be usedto create the buffer layers between the sensor layers. It is ideal tohave the sample chemicals enter the z-stack from the top of the stackand not from the side walls of the stack. To prevent unwanted intrusionin the sensor stack two methods can be used with stamping. First, is tostamp sensor layers between an impermeable blocking layers that aredefined by photolithograph which are impermeable to the chemicals thatare being sensed. The second method is to construct the layers in amanner where the over coating layers are larger in size and fully coverthe underlying layers eliminating any sidewalls. These two methods areseen in FIGS. 6a and 6b , where in FIG. 6a , 45 and 46 are stackedsensor layers and in intimate contact with them in the x and y directionare elements 42-44 which are impermeable blocking layers. In FIG. 6b theclosest sensor layer to the substrate 47 is then completely covered bythe next sensor layer 48 which is then completely covered the nextsensor layer 49 until the desired number of sensor layer is achieved.

Thermal evaporation of sensing layer can be achieved by multipledepositions of the sensing material on top of one another. The positionsof the sensing material is defined by shadow masking the sensorsubstrate.

Inkjet printing can also create stacked sensor layer structures by usingan immiscible solvent system with a buffer layer between sensors. Thisprocess involves printing the first layer such as a fluorescent polymerin an organic solvent like Chloroform. The next layer deposited wouldthen need to be in a solvent that will not perturb the underlying layersuch as a water solution of poly(diallydimethylammonium chloride). Thisprocess of immiscible solvent layers is then repeated until the desirednumber of sensor layer is achieved.

This system operates with a flow path of gas or liquid above the arrayof stacked sensors. Into that flow path pulses of samples are introducedto interact with the sensor. The sensors at each z level are monitoredin the same manner as traditional cross-reactive arrays where eachsensor's response in the array is analyzed, selecting characteristicfeatures from it. The features from each sensor are then aggregated tocreate a feature vector. The feature vector is then compared to knownfeature vectors to make sample identification. This invention bystacking sensor elements adds new information to the feature vector thatwas previously not measureable. The new information is difference intime from when vertically adjacent sensors start to respond. This timeis characteristic of how long it took of the analyte to pass through thetop sensor. The information added to the response pattern is thediffusion constants, and difference in time it takes for each sensor torespond. The diffusion constant and time delay are two characteristicfeatures that can be added to the response pattern for discrimination.The addition of non-responsive buffer layer between the sensor layersallows for tuning the time differential for chemicals passing throughthe stack of sensors improving the array discriminating ability. Alsoincreasing the resolving power for multicomponent samples.

It is obvious that many modifications and variations of the presentinvention are possible in light of the above teachings. It is thereforeto be understood that within the scope of the appended claims, theinvention may be practiced otherwise than as described.

What is claimed is:
 1. A multi-dimensional cross-reactive array forchemical sensing, comprising: a sensor substrate having stacks of sensorelements, wherein the sensor elements of a given stack are sequentiallystacked such that each stack of sensor elements rises in a z directionfrom a respective stack area as a unique sequence of sensor layers on anx-y surface of the sensor substrate; and an enclosure enclosing thesensor substrate such that a carrier medium carrying a chemical samplecan flow across the sequentially laid out stack areas on an x-y surfaceof the sensor substrate from one open end to another open end of theenclosure.
 2. The multi-dimensional cross-reactive array as recited inclaim 1, wherein said sensor substrate is based either on quartz foroptical based sensors or silicon for electrical based sensors.
 3. Themulti-dimensional cross-reactive array as recited in claim 1, whereinsaid carrier medium is either a gas or liquid sample carrier medium. 4.The multi-dimensional cross-reactive array as recited in claim 1,wherein said sensor elements are stacked in intimate contact one on topof another so that the only way for said sample chemical to interactwith underlying sensor elements is to pass by diffusion through thesensor element on top of it, whereby the stacking of the sensor elementsadds a time dependent response to the underlying sensor elements basedupon diffusion of the sample through the upper sensor layers.
 5. Themulti-dimensional cross-reactive array as recited in claim 1, wherein astack of sensor elements is based on its respective sequence of thefollowing fluorescent polymers layers:Poly[2,5-bisoctyloxy)-1,4-phenylenevinylene] with a emission between540-560 nm; Poly(9,9-dioctylfluorene-alt-benzothiadiazole) with emissionbetween 515-535 nm; andPoly[(9,9-dihexylfluoren-2,7-diyl)-co-(anthracen-9,10-diyl)] withemission between 450-435 nm.
 6. The multi-dimensional cross-reactivearray as recited in claim 1, wherein a sensor element in a stack isbased on a composite mix of fluorescent nanocrystals of a respectivenanocrystal size and a non-fluorescent polymer chosen from Poly(vinylstearate), Poly(benzyl methacrylate), Poly(methyl methacrylate) andPoly(ethylene-co-vinyl acetate).
 7. The multi-dimensional cross-reactivearray as recited in claim 1, wherein a stack of sensor elements is basedon a set of CdSe nanocrystals of sizes 2.2, 2.5 3.3, 4.5 nm withemission maxima of 480, 520, 560, 600 nm, respectively; a sensor layerbeing associated with a unique nanocrystal size so that different sensorlayers of the stack can be monitored independently.
 8. Themulti-dimensional cross-reactive array as recited in claim 1, wherein astack of sensor elements is based on a stack of chemiresistors with aninsulating buffer layer in between them, said chemiresistors beingchosen from a group consisting of modified carbon nanotubes, carbonnanotube polymer composites, and polymer carbon black composites.
 9. Themulti-dimensional cross-reactive array as recited in claim 1, wherein anon-responsive permeable buffer layer is added in between the sensorlayers to increase a migration time between sensors.
 10. Themulti-dimensional cross-reactive array as recited in claim 1, whereinthe sensor elements are stacked sequentially in a row along the flowpath.
 11. The multi-dimensional cross-reactive array as recited in claim1, wherein the sensor elements are z-stacked by stamping of thefluorescent polymer and/or polymer composite materials.
 12. Themulti-dimensional cross-reactive array as recited in claim 1, whereinthe sensor elements are z-stacked by inkjet printing of sensor layerswith a buffer layer between stacked sensors.
 13. A chemical sensingdevice based on a multi-dimensional cross-reactive array, comprising: amulti-dimensional cross-reactive array disposed along a flow path basedon a sensor substrate having a plurality of stacks of sensor elements,wherein the sensor elements of a stack are sequentially stacked suchthat a stack of sensor elements rises as a respective sequence offluorescent layers; a light source focused onto the multi-dimensionalcross-reactive array to cause each of the stacked sensor elements toemit a respective fluorescence; an optical system based on fiber opticcables for passing the respectively emitted light from each stack ofsensors to a respective spectrometer elements to produce a respectivespectrometer output; and a computing device connected to receive andprocess each spectrometer output for select wavelength bands tocharacterize each fluorescent layer in the sensor stack associated withthe respective spectrometer output throughout the array.
 14. Thechemical sensing device based on a multi-dimensional cross-reactivearray as recited in claim 13, wherein the light source is based on a 365nm LED.
 15. The chemical sensing device based on a multi-dimensionalcross-reactive array as recited in claim 13, wherein each fluorescentlayer in a sensor stack is an individually addressable polymer layerwith its associated spectrometer, each fluorescent polymer in a sensorstack yielding a distinct spectral characteristic to provide a robustcross-reactive array response.
 16. The chemical sensing device based ona multi-dimensional cross-reactive array as recited in claim 13, whereina sensor element in a stack is based on its fluorescentnanocrystal/polymer composite, wherein fluorescent emission isdetermined by its nanocrystal size.
 17. A method of chemical sensingbased on a multi-dimensional cross-reactive array, the method comprisingthe steps of: directing a flow path of a carrier medium carrying anunknown sample; disposing along the directed flow path amulti-dimensional cross-reactive array based on a sensor substratehaving a plurality of stacks of sensor elements, a sensor element in astack being based on a respective fluorescent layer; a light sourcefocused onto the multi-dimensional cross-reactive array to cause thestacked sensor elements to emit a respective fluorescence; passing viaan optical system the respective emissions of a stack of sensors to arespective spectrometer element to produce a respective spectrometeroutput; and receiving the spectrometer outputs by a computing device toprocess select wavelength bands to characterize each fluorescent polymeremissions per sensor stack associated with the respective spectrometeroutput to identify individual component samples and components in amixture sample.
 18. The method of chemical sensing according to claim17, wherein a fluorescent layer is based on any one of:Poly[2,5-bisoctyloxy)-1,4-phenylenevinylene] with a emission between540-560 nm; Poly(9,9-dioctylfluorene-alt-benzothiadiazole) with emissionbetween 515-535 nm; andPoly[(9,9-dihexylfluoren-2,7-diyl)-co-(anthracen-9,10-diyl)] withemission between 450-435 nm.
 19. The method of chemical sensingaccording to claim 17, wherein the spectrometer outputs are processedand select wavelength bands are monitored to characterize eachfluorescent emissions per sensor stack, thereby the respective polymersbeing individually addressable with a spectrometer associated with astack for a robust detection of cross-reactive array response.
 20. Themethod of chemical sensing according to claim 17, wherein the selectwavelength bands are processed by: generating a response vector based onmulti-sensor response patterns at each z level of sensors and time delayinformation from the sample passing from one level to the next; andusing the response vector to identify individual component samples andcomponents in a mixture sample.